ZNF502

Chr 3

zinc finger protein 502

NCBI Gene: 91392ENSG00000196653UniProt: Q8TBZ5

ZNF502 encodes a DNA-binding transcription factor that regulates gene expression by binding to specific DNA sequences and promoting transcription by RNA polymerase II. The gene shows minimal constraint against loss-of-function variants (LOEUF 1.138), and no definitive human disease associations have been established for ZNF502 mutations. Further research is needed to determine whether mutations in this transcriptional regulator cause pediatric neurological conditions.

ResearchSummary from RefSeq, UniProt
MultiplemechanismLOEUF 1.14
Clinical Summary— ZNF502
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
6 unique Pathogenic / Likely Pathogenic· 68 VUS of 79 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.14LOEUF
pLI 0.000
Z-score 1.11
OE 0.73 (0.48–1.14)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.62Z-score
OE missense 0.90 (0.81–0.99)
252 obs / 281.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.73 (0.48–1.14)
0≤0.351.4
Missense OE0.90 (0.81–0.99)
0≤0.61.4
Synonymous OE0.82
0≤1.21.6
LoF obs/exp: 14 / 19.2Missense obs/exp: 252 / 281.2Syn Z: 1.36
DN
0.91top 5%
GOF
0.85top 5%
LOF
0.2288th %ile

This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

DNprediction above median
GOFprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

79 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5
Likely Pathogenic1
VUS68
Likely Benign3
5
Pathogenic
1
Likely Pathogenic
68
VUS
3
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
5
0
5
Likely Pathogenic
0
0
1
0
1
VUS
0
66
2
0
68
Likely Benign
0
3
0
0
3
Benign
0
0
0
0
0
Total0698077

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ZNF502 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients